PMID- 30174308
OWN - NLM
STAT- MEDLINE
DCOM- 20191022
LR  - 20200309
IS  - 1932-7420 (Electronic)
IS  - 1550-4131 (Print)
IS  - 1550-4131 (Linking)
VI  - 28
IP  - 6
DP  - 2018 Dec 4
TI  - Functional Gut Microbiota Remodeling Contributes to the Caloric 
      Restriction-Induced Metabolic Improvements.
PG  - 907-921.e7
LID - S1550-4131(18)30506-0 [pii]
LID - 10.1016/j.cmet.2018.08.005 [doi]
AB  - Caloric restriction (CR) stimulates development of functional beige fat and 
      extends healthy lifespan. Here we show that compositional and functional changes 
      in the gut microbiota contribute to a number of CR-induced metabolic improvements 
      and promote fat browning. Mechanistically, these effects are linked to a lower 
      expression of the key bacterial enzymes necessary for the lipid A biosynthesis, a 
      critical lipopolysaccharide (LPS) building component. The decreased LPS dictates 
      the tone of the innate immune response during CR, leading to increased eosinophil 
      infiltration and anti-inflammatory macrophage polarization in fat of the 
      CR animals. Genetic and pharmacological suppression of the LPS-TLR4 pathway or 
      transplantation with Tlr4(-/-) bone-marrow-derived hematopoietic cells increases 
      beige fat development and ameliorates diet-induced fatty liver, while Tlr4(-/-) 
      or microbiota-depleted mice are resistant to further CR-stimulated metabolic 
      alterations. These data reveal signals critical for our understanding of the 
      microbiota-fat signaling axis during CR and provide potential new anti-obesity 
      therapeutics.
CI  - Copyright (c) 2018 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Fabbiano, Salvatore
AU  - Fabbiano S
AD  - Department of Cell Physiology and Metabolism, Centre Medical Universitaire, 
      Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland; Diabetes 
      Centre, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland.
FAU - Suarez-Zamorano, Nicolas
AU  - Suarez-Zamorano N
AD  - Department of Cell Physiology and Metabolism, Centre Medical Universitaire, 
      Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland; Diabetes 
      Centre, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland.
FAU - Chevalier, Claire
AU  - Chevalier C
AD  - Department of Cell Physiology and Metabolism, Centre Medical Universitaire, 
      Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland; Diabetes 
      Centre, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland.
FAU - Lazarevic, Vladimir
AU  - Lazarevic V
AD  - Genomic Research Lab, Division of Infectious Diseases, Geneva University 
      Hospitals, 1211 Geneva, Switzerland.
FAU - Kieser, Silas
AU  - Kieser S
AD  - Department of Cell Physiology and Metabolism, Centre Medical Universitaire, 
      Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland; Diabetes 
      Centre, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland.
FAU - Rigo, Dorothee
AU  - Rigo D
AD  - Department of Cell Physiology and Metabolism, Centre Medical Universitaire, 
      Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland; Diabetes 
      Centre, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland.
FAU - Leo, Stefano
AU  - Leo S
AD  - Genomic Research Lab, Division of Infectious Diseases, Geneva University 
      Hospitals, 1211 Geneva, Switzerland.
FAU - Veyrat-Durebex, Christelle
AU  - Veyrat-Durebex C
AD  - Department of Cell Physiology and Metabolism, Centre Medical Universitaire, 
      Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland; Diabetes 
      Centre, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland.
FAU - Gaia, Nadia
AU  - Gaia N
AD  - Genomic Research Lab, Division of Infectious Diseases, Geneva University 
      Hospitals, 1211 Geneva, Switzerland.
FAU - Maresca, Marcello
AU  - Maresca M
AD  - Discovery Biology, Discovery Sciences, IMED Biotech Unit, AstraZeneca Gothenburg, 
      Molndal 43183, Sweden.
FAU - Merkler, Doron
AU  - Merkler D
AD  - Department of Pathology and Immunology, Centre Medical Universitaire, Faculty of 
      Medicine, University of Geneva, 1211 Geneva, Switzerland.
FAU - Gomez de Aguero, Mercedes
AU  - Gomez de Aguero M
AD  - Maurice Muller Laboratories (DKF), Universitatsklinik fur Viszerale Chirurgie und 
      Medizin Inselspital, University of Bern, 3010 Bern, Switzerland.
FAU - Macpherson, Andrew
AU  - Macpherson A
AD  - Maurice Muller Laboratories (DKF), Universitatsklinik fur Viszerale Chirurgie und 
      Medizin Inselspital, University of Bern, 3010 Bern, Switzerland.
FAU - Schrenzel, Jacques
AU  - Schrenzel J
AD  - Genomic Research Lab, Division of Infectious Diseases, Geneva University 
      Hospitals, 1211 Geneva, Switzerland.
FAU - Trajkovski, Mirko
AU  - Trajkovski M
AD  - Department of Cell Physiology and Metabolism, Centre Medical Universitaire, 
      Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland; Diabetes 
      Centre, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland; 
      Institute of Genetics and Genomics in Geneva, University of Geneva, 1211 Geneva, 
      Switzerland. Electronic address: mirko.trajkovski@unige.ch.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180830
PL  - United States
TA  - Cell Metab
JT  - Cell metabolism
JID - 101233170
RN  - 0 (Bacterial Proteins)
RN  - 0 (Lipid A)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
SB  - IM
MH  - Adipose Tissue, Beige/cytology/*metabolism
MH  - Animals
MH  - Bacterial Proteins/*metabolism
MH  - *Caloric Restriction
MH  - Eosinophils/immunology
MH  - Fatty Liver/*metabolism
MH  - *Gastrointestinal Microbiome
MH  - *Gastrointestinal Tract/immunology/microbiology
MH  - Lipid A/*metabolism
MH  - Macrophages/immunology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Toll-Like Receptor 4/metabolism
PMC - PMC6288182
OTO - NOTNLM
OT  - TLR4
OT  - beige fat
OT  - browning
OT  - caloric restriction
OT  - fatty liver
OT  - gut microbiota
OT  - innate immunity
OT  - insulin sensitivity
EDAT- 2018/09/04 06:00
MHDA- 2019/10/23 06:00
PMCR- 2018/12/04
CRDT- 2018/09/04 06:00
PHST- 2018/06/01 00:00 [received]
PHST- 2018/07/13 00:00 [revised]
PHST- 2018/08/02 00:00 [accepted]
PHST- 2018/09/04 06:00 [pubmed]
PHST- 2019/10/23 06:00 [medline]
PHST- 2018/09/04 06:00 [entrez]
PHST- 2018/12/04 00:00 [pmc-release]
AID - S1550-4131(18)30506-0 [pii]
AID - 10.1016/j.cmet.2018.08.005 [doi]
PST - ppublish
SO  - Cell Metab. 2018 Dec 4;28(6):907-921.e7. doi: 10.1016/j.cmet.2018.08.005. Epub 
      2018 Aug 30.